This proposal is directed toward a further understanding of the genetic, developmental, and molecular bases of hereditary infections in higher organisms. The particular systems under investigation, involving eukaryote hosts (species of flies of the genus Drosophila) and transovarially transmitted agents (micro-organisms, viruses), express themselves phenotypically as the absence, or extreme reduction in number, of males in the progenies of affected females. This abnormal condition is referred to as maternal "sex-ratio" or SR. Unisexual progenies are a consequence of male mortality at early developmental stages, usually embryonic. Cases of maternal SR fall into two groups: those in neotropical species which are readily transferable by hemolymph injection into normal females of the same or different species; and those in palearctic and nearctic species, so far refractory to such transfer. The transmitted agents in the former are small, spiral, wall-free prokaryotes now referred to as SR-spiroplasmas; those in the latter remain uncharacterized and require investigation. Questions toward which the project is directed include: what are the molecular genetic bases for differences in the developmental physiology of the sexes which lead to the benign transmission of infectious agents in females on the one hand and to the disruption of development of male zygotes on the other? What is the nature of the effective androcidal agent and its mode of action? What are the bases for differences in patterns of expression by SR-spiroplasmas of different origin when introduced into the same strain or species of fly? Viruses small phages associated with the SR-spiroplasmas, making them lysogenic, serve as tools as well as materials when combined with the methods of genetics, cytology, and molecular biology in seeking answers to these questions.